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Report documents rabies transmission from organ transplant

University of Michigan infectious disease expert urges physicians to be aware of risk, protect organ recipients

CHICAGO – An investigation into the source of a fatal case of raccoon rabies virus exposure showed the individual received the virus via a kidney transplant 18 months earlier, according to a study in the July 24/31 Journal of the American Medical Association.

Dr. Daniel Kaul, director of the Transplant Infectious Disease Service at the University of Michigan Health System

The case did not involve a University of Michigan patient, but in a JAMA editorial Daniel R. Kaul, M.D., director of the Transplant Infectious Disease Service at the U-M Health System, describes the best steps for preventing future infections among the thousands waiting for life-saving organs.

Although solid organ transplant transmission of infectious encephalitis is rare, the findings suggest that rabies transmitted by this route may have a long incubation period and further education to increase awareness is needed.

The rabies virus causes a fatal encephalitis (inflammation of the brain) and can be transmitted through tissue or organ transplantation.

“Unique rabies virus variants, distinguishable by molecular typing methods, are associated with specific animal reservoirs. Globally, an estimated 55,000 persons die of rabies every year, with most transmission attributable to dog bites. Approximately two human rabies deaths are reported in the United States every year and during 2000 through 2010, all but two domestically acquired cases were associated with bats.

"Despite raccoons being the most frequently reported rabid animal in the United States, only one human rabies case associated with the raccoon rabies virus variant has been reported,” according to background information in the article. In February 2013, a kidney recipient with no reported exposures to potentially rabid animals died from rabies 18 months after transplantation.

Neil M. Vora, M.D., of the Centers for Disease Control and Prevention, Atlanta, and colleagues conducted a study to determine whether organ transplantation was the source of rabies virus exposure in the kidney recipient, and to evaluate for and prevent rabies in other transplant recipients who obtained a kidney, heart, and liver from the same donor.

Organ donor and all transplant recipient medical records were reviewed. Laboratory tests to detect rabies virus-specific binding antibodies, rabies virus neutralizing antibodies, and rabies virus antigens were conducted on available specimens, including serum, cerebrospinal fluid, and tissues from the donor and the recipients.

The researchers found that in retrospect, the kidney donor's symptoms prior to death were consistent with rabies, and not what was presumed to be a foodborne illness. Subsequent interviews with family members revealed that the donor had significant wildlife exposure, and had sustained at least two raccoon bites, for which he did not seek medical care. Rabies virus antigen was detected in archived autopsy brain tissue collected from the donor.

The rabies viruses infecting the donor and the deceased kidney recipient were consistent with the raccoon rabies virus variant and were more than 99.9 percent identical across the entire N gene, thus confirming organ transplantation as the route of transmission.

The three other organ recipients did not have signs or symptoms consistent with rabies or encephalitis. They have remained asymptomatic, with rabies virus neutralizing antibodies detected in their serum after completion of postexposure prophylaxis.

“This transmission event provides an opportunity for enhancing rabies awareness and recognition and highlights the need for a modified approach to organ donor screening and recipient monitoring for infectious encephalitis. This investigation also underscores the importance of collaboration between clinicians, epidemiologists, and laboratory scientists,” the authors write.

In an accompanying editorial, Kaul, an associate professor of internal medicine at the University of Michigan Medical School, writes that during the past decade, numerous instances have been reported of donor-derived infection among recipients of solid organ transplants with pathogens associated with central nervous system (CNS) infections, including the West Nile virus and rabies virus.

“Educational efforts to improve recognition of donors with CNS infection and the risks associated with using these donors should be directed not just at the transplant community but at the larger community of physicians involved in the care of potential donors—particularly critical care specialists, neurologists, and infectious disease physicians.

”These clinicians may not be aware of the potential for donor-derived infection, but accepting transplant centers must rely on the clinical impression of those caring for the potential donor. Although the risk of donor-derived disease is inherent in the process of organ transplantation and cannot be eliminated, raising awareness of the risk of using donors with undiagnosed CNS infection is the best way to reduce the occurrence of these transmissions.”

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